松香基N-杂环卡宾催化不对称反应机理及构效关系研究

Based on green environmental protection and sustainable development requirements, the development of highly efficient and low toxicity of natural chiral catalyst becomes very urgent and important. In this proposal, natural products rosin and its derivatives are chosen as the main raw materials. Then a series of rosin-based N-heterocyclic carbene (NHC) molecules with different link structures are designed and synthesized. The theoretical chemistry methods are used to investigate the mechanism of two classical asymmetric reactions catalyzed by the novel rosin-based NHCs (Stetter reaction and spirocyclic butyrolactone cyclization reaction). Some factors such as electrostatic effect and spatial effect of catalyst molecules on the reaction stereoselectivity are further studied. How the three-dimensional rigid structures and chiral centers of the rosin to regulate the reaction stereoselectivity are especially focused. Meanwhile, the structure-property relationship models between catalytic activity of asymmetric reactions and molecular structures of rosin-based NHCs are established by theoretical studies of quantum chemical calculation. According to models developed in this project, how rosin-based NHC molecular descriptors affect the catalytic activity would be revealed. On the basis of results obtained from above studies, related conclusions would supply guidance in the design of new more rosin-based chiral catalysts, and lay a foundation for applications of rosin-based NHC in asymmetric catalysis field.

基于绿色环保、可持续发展的要求，开发高效低毒的天然手性源催化剂就变得非常紧迫和重要。本课题以天然产物松香及其衍生物为主要原料，设计合成不同官能团连接的松香基NHC分子。通过理论化学方法，研究新型松香基NHC分子催化Stetter反应和螺环丁内酯环合反应两种经典不对称反应的作用机理，进一步探讨催化剂分子的静电效应和空间效应等因素对反应立体选择性的影响，着重考察松香骨架的刚性立体结构和手性中心对反应立体选择性的调控。通过理论研究中的量子化学计算方法建立松香基NHC催化不对称反应活性与分子结构的定量关系模型，分析影响催化剂活性的分子结构描述符，进一步揭示松香基NHC催化不对称反应的机理，从而为高效松香基催化剂的设计合成提供理论指导。通过上述研究，为松香基NHC在不对称催化领域的应用奠定基础。

基于绿色环保、可持续发展的要求，以资源丰富，可再生的天然产物松香及其衍生物作为主要原料，设计合成了酰胺基团链接的松香基（脱氢枞基和丙烯海松基）新型NHC催化剂分子。以制备的新型松香基NHC分子催化了芳香醛和芳基硼酸的加成反应和螺环丁内酯环合反应，分别得到目标产物二芳基甲醇和螺环丁内酯吲哚酮衍生物。通过考察催化剂的用量、反应时间、温度、溶剂以及添加的酸/碱等对反应的影响来筛选催化剂和进行活性评价；同时通过理论化学方法对松香基NHC催化芳香醛和芳基硼酸的加成反应的作用机理以及松香基NHC催化螺环丁内酯吲哚酮的立体选择性进行了研究;建立了丙烯海松基NHC催化剂分子反应活性与反应收率的定量构效关系模型，探索了催化剂分子的结构描述符与催化活性之间的线性回归关系，进一步丰富了松香基NHC催化加成反应机理的研究以及高效催化剂分子的合成设计。